Studies of the metabolic stability in cells of 5-(trifluoroacetyl)thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors.
5-(Trifluoroacetyl)thiophene-2-carboxamides were found to be potent and selective class II HDAC inhibitors. This paper describes their further development and the investigation on the cause for the lack of cell-based activity. A rapid screening assay was set up which enabled the identification of more metabolic stable compounds as potent and selective class II HDAC inhibitors.
Scarpelli
Rita
R
IRBM-Merck Research Laboratories Rome, Via Pontina km 30,600, Pomezia 00040, Rome, Italy. rita_scarpelli@merck.com
Di Marco
Annalise
A
Ferrigno
Federica
F
Laufer
Ralph
R
Marcucci
Isabella
I
Muraglia
Ester
E
Ontoria
Jesus M
JM
Rowley
Michael
M
Serafini
Sergio
S
Steinkühler
Christian
C
Jones
Philip
P
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D065729:Cytochrome P-450 CYP2C9; D015195:Drug Design; D045325:HCT116 Cells; D006367:HeLa Cells; D022781:Hepatocytes / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000145:classification; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects
D000577:Amides; D056572:Histone Deacetylase Inhibitors; D013876:Thiophenes; D014404:Tubulin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D006655:Histone Deacetylases